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PMID: 24843134 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P2 and maintenance of KCNQ2/3 ion channel current.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 111 ·No. 22 ·2014-06-03 ·Pages E2281-90

Dickson EJ, Jensen JB, Hille B

Abstract

Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 domains as real-time indicators of PM PI(4,5)P2, and translocation of PHOSH2×2, and PHOSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P2. Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P2. The decline of PI(4,5)P2 following 4-phosphatase recruitment takes 1-2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI(4,5)P2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity.

Keywords
phosphoinositides pleckstrin homology domain wortmannin
MeSH Terms
1-Phosphatidylinositol 4-Kinase/metabolism Androstadienes/pharmacology Cell Membrane/metabolism Cells, Cultured Golgi Apparatus/metabolism Humans KCNQ2 Potassium Channel/physiology KCNQ3 Potassium Channel/physiology Kidney/cytology Membrane Potentials/physiology Myosin Type II/metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphatidylinositols/metabolism Protein Kinase Inhibitors/pharmacology Wortmannin
Chemicals
Androstadienes KCNQ2 Potassium Channel KCNQ2 protein, human KCNQ3 Potassium Channel KCNQ3 protein, human Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositols Protein Kinase Inhibitors 1-Phosphatidylinositol 4-Kinase Myosin Type II Wortmannin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dickson Eamonn J
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Jensen Jill B
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Hille Bertil
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195 [email protected].
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1407133111
Email
[email protected]
Published
2014-06-03
Epub
2014-00-19
Pages
E2281-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC4050574
Subset
IM
Grants
NINDS NIH HHS · R37 NS008174 · United States
NINDS NIH HHS · R37NS008174 · United States
External Links
PubMed source DOI: 10.1073/pnas.1407133111 PMC Full Text View journal details
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